Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as "yarrow" and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints. AIM OF THE STUDY: In the present study, we evaluated the efficacy of a hydroalcoholic extract from the Achillea millefolium (HE) for gastroprotective properties and additional mechanism(s) involved in this activity. MATERIAL AND METHODS: Rats were treated with HE and subsequently exposed to both acute gastric lesions induced by ethanol P.A. and chronic gastric ulcers induced by 80% acetic acid. Following treatment, glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured. The activity of myeloperoxidase (MPO) and histological and immunohistochemical analysis were performed in animals with acetic acid-induced gastric ulcers. RESULTS: Oral administration of HE (30, 100 and 300mg/kg) inhibited ethanol-induced gastric lesions by 35, 56 and 81%, respectively. Oral treatment with HE (1 and 10mg/kg) reduced the chronic gastric ulcers induced by acetic acid by 43 and 65%, respectively, and promoted significant regeneration of the gastric mucosa after ulcer induction denoting increased cell proliferation, which was confirmed by PCNA immunohistochemistry. HE treatment prevented the reduction of GSH levels and SOD activity after acetic acid-induced gastric lesions. In addition, HE (10mg/kg) inhibited the MPO activity in acetic acid-induced gastric ulcers. CONCLUSIONS: The results of the present study indicate that the antioxidant properties of HE may contribute to the gastroprotective activity of this extract.